40 CFR 158.2083 - Experimental use permit biochemical pesticides human health assessment data requirements table.

Regulations last checked for updates: Nov 22, 2024

Title 40 - Protection of Environment last revised: Nov 20, 2024

Collapse to view only § 158.2083 - Experimental use permit biochemical pesticides human health assessment data requirements table.

Table of Contents

§ 158.2000 - Biochemical pesticides definition and applicability.

§ 158.2010 - Biochemical pesticides data requirements.

§ 158.2030 - Biochemical pesticides product chemistry data requirements table.

§ 158.2040 - Biochemical pesticides residue data requirements table.

§ 158.2050 - Biochemical pesticides human health assessment data requirements table.

§ 158.2060 - Biochemical pesticides nontarget organisms and environmental fate data requirements table.

§ 158.2070 - Biochemical pesticides product performance data requirements.

§ 158.2080 - Experimental use permit data requirements—biochemical pesticides.

§ 158.2081 - Experimental use permit biochemical pesticides product chemistry data requirements table.

§ 158.2082 - Experimental use permit biochemical pesticides residue data requirements table.

§ 158.2083 - Experimental use permit biochemical pesticides human health assessment data requirements table.

§ 158.2084 - Experimental use permit biochemical pesticides nontarget organisms and environmental fate data requirements table.

§ 158.2000 - Biochemical pesticides definition and applicability.

This subpart applies to all biochemical pesticides as defined in paragraphs (a), (b), and (c) of this section.

(a) Definitions. The following terms are defined for the purposes of subpart U of this part.

(1) A biochemical pesticide is a pesticide that:

(i) Is a naturally-occurring substance or structurally-similar and functionally identical to a naturally-occurring substance;

(ii) Has a history of exposure to humans and the environment demonstrating minimal toxicity, or in the case of a synthetically-derived biochemical pesticides, is equivalent to a naturally-occurring substance that has such a history; and

(iii) Has a non-toxic mode of action to the target pest(s).

(2) A Pheromone is a compound produced by a living organism or is a synthetically derived substance that is structurally similar and functionally identical to a naturally-occurring pheromone, which, alone or in combination with other such compounds, modifies the behavior of other individuals of the same species.

(i) An Arthropod Pheromone is a pheromone produced by a member of the taxonomic phylum Arthropoda.

(ii) A Lepidopteran Pheromone is an arthropod pheromone produced by a member of the insect order Lepidoptera.

(iii) A Straight Chain Lepidopteran Pheromone is a lepidopteran pheromone consisting of an unbranched aliphatic chain (between 9 and 18 carbons) ending in an alcohol, aldehyde, or acetate functional group and containing up to three double bonds in the aliphatic backbone.

(b) Examples. Biochemical pesticides include, but are not limited to:

(1) Semiochemicals (insect pheromones and kairomones),

(2) Natural plant and insect regulators,

(3) Naturally-occurring repellents and attractants, and

(4) Enzymes.

(c) Applicability. The Agency may review, on a case-by-case basis, naturally-occurring pesticides that do not clearly meet the definition of a biochemical pesticide in an effort to ensure, to the greatest extent possible, that only the minimum testing sufficient to make scientifically sound regulatory decisions would be conducted. The Agency will review applications for registration of naturally-occurring pesticides to determine whether to review the pesticide under this subpart U.

§ 158.2010 - Biochemical pesticides data requirements.

(a) Sections 158.2030 through 158.2070 identify the data requirements that are required to support registration of biochemical pesticides. Sections 158.2080 through 158.2084 identify the data requirements that are required to support Experimental Use Permits (EUPs). Variations in the test conditions are identified within the test notes. Definitions that apply to all biochemical data requirements can be found in § 158.2000.

(b) Each data table includes “use patterns” under which the individual data are required, with variations including food and nonfood uses for terrestrial and aquatic applications, greenhouse, indoor, forestry, and residential outdoor applications under certain circumstances.

(c) The categories for each data requirement are “R”, which stands for required, and “CR” which stands for conditionally required. Generally, “R” indicates that the data are more likely required than for those data requirements with “CR.” However, in each case, the regulatory text preceding the data table and the test notes following the data table must be used to determine whether the data requirement must be satisfied.

(d) Each table identifies the test substance that is required to be tested to satisfy the data requirement. Test substances may include: technical grade active ingredient (TGAI), manufacturing-use product (MP), end-use product (EP), typical end-use product (TEP), residue of concern, and pure active ingredient (PAI) or all of the above (All). Commas between the test substances (i.e., TGAI, EP) indicate that data may be required on the TGAI or EP or both depending on the conditions set forth in the test note.

(e) The data requirements are organized into a tier-testing system with specified additional studies at higher tiers being required if warranted by adverse effects observed in lower tier studies. The lower tier studies are a subset of those required for conventional pesticides, and the studies overall are generally selected from those required for conventional pesticides.

(f) Two sets of guideline numbers are provided for some of the environmental fate data requirements. For ease of understanding, the current guidelines will be used as an interim measure until the new guidelines (in parentheses) are finalized.

§ 158.2030 - Biochemical pesticides product chemistry data requirements table.

(a) General. (1) Sections 158.100 through 158.130 describe how to use this table to determine the product chemistry data requirements for a particular pesticide product. Notes that apply to an individual test and include specific conditions, qualifications, or exceptions to the designated test are listed in paragraph (e) of the section.

(2) Definitions in § 158.300 apply to data requirements in this section.

(b) Use patterns. Product chemistry data are required for all pesticide products and are not use specific.

(d) Table. The following table shows the data requirements for biochemical pesticides product chemistry. The test notes are shown in paragraph (e) of this section.

Table—Biochemical Pesticides Product Chemistry Data Requirements

Guideline Number	Data Requirement	All Use Patterns	Test Substance		Test Notes
Guideline Number	Data Requirement	All Use Patterns	MP	EP	Test Notes
Product Identity and Composition
880.1100	Product identity and composition	R	TGAI, MP	TGAI, EP	1, 2
880.1200	Description of starting materials, production and formulation process	R	TGAI, MP	TGAI, EP	2, 3
880.1400	Discussion of formation of impurities	R	TGAI and MP	TGAI and EP	4
Analysis and Certified Limits
830.1700	Preliminary analysis	CR	TGAI and MP	TGAI and EP	5, 8
830.1750	Certified limits	R	MP	EP	6
830.1800	Enforcement analytical method	R	MP	EP	7
Physical and Chemical Characteristics
830.6302	Color	R	TGAI	TGAI	8
830.6303	Physical state	R	TGAI and MP	TGAI and EP	8
830.6304	Odor	R	TGAI	TGAI	8
830.6313	Stability to normal and elevated temperatures, metals and metal ions	R	TGAI	TGAI	8, 17
830.6315	Flammability	CR	MP	EP	9
830.6317	Storage stability	R	MP	EP	—
830.6319	Miscibility	CR	MP	EP	10
830.6320	Corrosion characteristics	R	MP	EP	—
830.7000	pH	CR	TGAI and MP	TGAI and EP	8, 11
830.7050	UV/Visible light absorption	R	TGAI	TGAI	—
830.7100	Viscosity	CR	MP	EP	12
830.7200	Melting point/melting range	CR	TGAI	TGAI	8, 13
830.7220	Boiling point/boiling range	CR	TGAI	TGAI	8, 14
830.7300	Density/relative density/bulk density	R	TGAI and MP	TGAI and EP	8, 18
830.7520	Particle size, fiber length, and diameter distribution	CR	TGAI	TGAI	8, 15
830.7550 830.7560 830.7570	Partition coefficient (n-Octanol /Water)	CR	TGAI	TGAI	16
830.7840	Water solubility	R	TGAI	TGAI	8
830.7950	Vapor pressure	R	TGAI	TGAI	8, 19

(e) Test notes. The following test notes are applicable to the data requirements for biochemical pesticides product chemistry and are referenced in the last column of the table in paragraph (d) of this section.

1. Data must be provided in accordance with § 158.320.

2. If the MP and EP are produced by an integrated formulation system (non-registered source), these data are also required on TGAI.

3. Data must be provided in accordance with §§ 158.325, 158.330, and § 158.335.

4. Data must be provided in accordance with § 158.340.

6. Data must be provided in accordance with § 158.350.

7. Data must be provided in accordance with § 158.355.

8. If the TGAI cannot be isolated, data are required on the practical equivalent of the TGAI. EP testing may also be appropriate.

9. Required if the product contains combustible liquids.

10. Required if the product is an emulsifiable liquid and is to be diluted with petroleum solvents.

11. Required if the test substance is soluble or dispersible in water.

12. Required if the product is a liquid.

13. Required when the technical chemical is a solid at room temperature.

14. Required when the technical chemical is a liquid at room temperature.

15. Required for water insoluble test substances (>10−6g/l) and fibrous test substances with diameter ≥0.1 µm.

16. Required for organic chemicals unless they dissociate in water or are partially or completely soluble in water.

17. Data on the stability to metals and metal ions is required only if the active ingredient is expected to come in contact with either material during storage.

18. True density or specific density are required for all test substances. Data on bulk density is required for MPs or EPs that are solid at room temperature.

19. Not required for salts.

§ 158.2040 - Biochemical pesticides residue data requirements table.

(a) General. Sections 158.100 through 158.130 describe how to use this table to determine the biochemical pesticides residue data requirements for a particular pesticide product and the substance that needs to be tested. These data requirements apply to all biochemical pesticides, i.e., naturally occurring insect repellents and attractants, semiochemicals (e.g., insect pheromones), natural and plant growth regulators. Notes that apply to an individual test and include specific conditions, qualifications, or exceptions to the designated test are listed in paragraph (e) of this section.

(b) Use patterns. (1) Data are required or conditionally required for all pesticides used in or on food and for residential outdoor uses where food crops are grown. Food use patterns include products classified under the general use patterns of terrestrial food crop use, terrestrial feed crop use, aquatic food crop use, greenhouse food crop use, and indoor food use. Data are also conditionally required for aquatic nonfood use if there is direct application to water that could subsequently result in exposure to food.

(2) Data are conditionally required for nonfood uses if pesticide residues may occur in food or feed as a result of the use. Data requirements for these nonfood uses would be determined on a case-by-case basis. For example, most products used in or near kitchens require residue data for risk assessment purposes even though tolerances may not be necessary in all cases.

(c) Key. R = Required; CR = Conditionally required; NR = Not required; MP = Manufacturing end-use product; EP = End-use product; TEP = Typical end-use product; TGAI = Technical grade of the active ingredient; Residue of concern = the active ingredient and its metabolites, degradates, and impurities of toxicological concern; All = All of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph (e) of this section, and apply to the individual tests in the following table:

(d) Data requirements table. The following table shows the data requirements for biochemical pesticides residue. The test notes are shown in paragraph (e) of this section.

Table—Biochemical Residue Data Requirements for Specific Uses

Guideline Number	Data Requirement	Use Patterns				Test Substance	Test Notes
		Terrestrial	Aquatic	Greenhouse Food	Indoor Food
		Food/Feed	Food	Greenhouse Food	Indoor Food
Supporting Information
860.1100	Chemical identity	CR	CR	CR	CR	TGAI	1, 2, 4
860.1200	Directions for use	CR	CR	CR	CR	—	1, 3, 4
Nature of the Residue
860.1300	Nature of the residue in plants	CR	CR	CR	CR	TGAI	1, 4, 5, 6
860.1300	Nature of the residue in livestock	CR	CR	CR	CR	TGAI or plant metabolite	1, 7, 8, 10, 13
860.1340	Residue analytical method	CR	CR	R	CR	Residue of concern	4, 9, 10
860.1360	Multiresidue method	CR	CR	R	CR	Residue of concern	10, 11
Magnitude of the Residue
860.1400	Potable water	NR	CR	NR	NR	TGAI	1, 12
860.1400	Fish	NR	CR	NR	NR	TGAI	1, 13
860.1400	Irrigated crops	NR	CR	NR	NR	TGAI	1, 14
860.1460	Food handling	NR	NR	NR	CR	TGAI	1, 15
860.1480	Meat/milk/poultry/eggs	CR	CR	CR	CR	TGAI or plant metabolites	1, 7, 8, 10
860.1500	Crop field trials	CR	CR	CR	CR	TEP	1, 3, 4
860.1520	Processed food/feed	CR	CR	CR	CR	TEP	1, 16
860.1540	Anticipated residues	CR	CR	CR	CR	Residue of concern	1, 10, 17
860.1550	Proposed tolerances	CR	CR	CR	CR	—	1, 18
860.1560	Reasonable grounds in support of the petition	CR	CR	CR	CR	—	1, 10
860.1650	Submittal of analytical reference standards	CR	CR	CR	CR	TGAI and residue of concern	10, 19

(e) Test notes. The following test notes are applicable to the data requirements for biochemical pesticides product chemistry and are in the last column of the table contained in paragraph (d) of this section.

1. Residue chemistry data requirements apply to biochemical pesticide products when Tier II or Tier III toxicology data are required, as specified for biochemical agents in the biochemical human health assessment data requirements, § 158.2050.

2. The same chemical identity data are required for biochemical product chemistry data requirements, § 158.2030, with an emphasis on impurities.

3. Required information includes crops to be treated, rate of application, number and timing of applications, preharvest intervals, and relevant restrictions.

4. Required for residential outdoor uses on food crops if the corresponding agricultural use is not approved or the residential use is expected to produce higher residues based on the label directions.

5. Required unless it is an arthropod pheromone applied at a rate less than or equal to 150 grams active ingredient per acre.

6. Required for indoor uses where the pesticide is applied directly to food, in order to determine metabolites and/or degradates. Not required when only indirect contact with food would occur (e.g., crack and crevice treatments).

7. Required when a pesticide is to be applied directly to livestock, to livestock premises, to livestock drinking water, or to crops used for livestock feed.

8. If results from the plant metabolism study show differing metabolites in plants from those found in animals, an additional livestock metabolism study involving dosing with the plant metabolite(s) may also be required.

9. A residue analytical method suitable for enforcement of tolerances is required whenever a numeric tolerance (including temporary and time-limited tolerances) is proposed.

10. Required if indoor use could result in pesticide residues in or on food or feed.

11. Data are required to determine whether FDA/USDA multiresidue methodology would detect and identify the pesticides and any metabolites.

12. Data are required whenever a pesticide may be applied directly to water, unless it can be demonstrated that the treated water would not be available for human or livestock consumption.

13. Data on fish are required for all pesticides applied directly to water inhabited, or which will be inhabited by fish that may be caught or harvested for human consumption.

14. Data are required when a pesticide is to be applied directly to water that could be used for irrigation or to irrigation facilities such as irrigation ditches.

15. Data are required whenever a pesticide may be used in food/feed handling establishments.

16. Data on the nature and level of residue in processed food/feed are required when detectible residues could potentially concentrate on processing thus requiring the establishment of a separate tolerance higher than that of the raw agricultural commodity.

17. Required when residues at the tolerance level may result in risk of concern. These data may include washing, cooking, processing, or degradation studies as well as market basket surveys for a more precise residue determination.

18. The proposed tolerance must reflect the maximum residue likely to occur in crops, in meat, milk, poultry, or eggs.

19. Required when a residue analytical method is required.

§ 158.2050 - Biochemical pesticides human health assessment data requirements table.

(a) General. (1) Sections 158.100 through 158.130 describe how to use this table to determine the biochemical human health assessment data requirements for a particular biochemical pesticide product.

(2) The data in this section are not required for straight chain lepidopteran pheromones when applied up to a maximum use rate of 150 grams active ingredient/acre/year.

(b) Use patterns. (1) Food use patterns, in general, include products classified under the following general uses: terrestrial food crop use; terrestrial feed crop use; aquatic food crop use; greenhouse food crop use.

(2) Nonfood use patterns include products classified under the general use patterns of terrestrial nonfood crop use; aquatic nonfood residential use; aquatic nonfood outdoor use; aquatic nonfood industrial use; greenhouse nonfood crop use; forestry use; residential outdoor use; residential indoor use; indoor food use; indoor nonfood use; indoor medical use.

(c) Key. R = Required; CR = Conditionally required; NR = Not required; MP = Manufacturing-use product; EP = End-use product; TEP = Typical end-use product; TGAI = Technical grade of the active ingredient; Residue of concern = the active ingredient and its metabolites, degradates, and impurities of toxicological concern; All = All of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph (e) of this section, and apply to the individual tests in the following table:

(d) Table. The following table shows the data requirements for biochemical pesticides human health assessment. The test notes are shown in paragraph (e) of this section.

Table—Biochemical Pesticides Human Health Assessment Data Requirements

Guideline Number	Data Requirement	Use Patterns		Test Substance		Test Notes
Guideline Number	Data Requirement	Food	Nonfood	MP	EP	Test Notes
Tier I
Acute Testing
870.1100	Acute oral toxicity - rat	R	R	TGAI and MP	TGAI and EP	1
870.1200	Acute dermal toxicity	R	R	TGAI and MP	TGAI and EP	1, 2
870.1300	Acute inhalation toxicity - rat	R	R	TGAI and MP	TGAI and EP	3
870.2400	Primary eye irritation - rabbit	R	R	TGAI and MP	TGAI and EP	2
870.2500	Primary dermal irritation	R	R	TGAI and MP	TGAI and EP	1, 2
870.2600	Dermal sensitization	R	R	TGAI and MP	TGAI and EP	2, 4
none	Hypersensitivity incidents	R	R	All	All	5
Subchronic Testing
870.3100	90-day oral (one species)	R	CR	TGAI	TGAI	6
870.3250	90-day dermal - rat	CR	CR	TGAI	TGAI	7
870.3465	90-day inhalation - rat	CR	CR	TGAI	TGAI	8
Developmental Toxicity
870.3700	Prenatal developmental - rat preferably	R	CR	TGAI	TGAI	9
Mutagenicity Testing
870.5100	Bacterial reverse mutation test	R	CR	TGAI	TGAI	10
870.5300 870.5375	In vitro mammalian cell assay	R	CR	TGAI	TGAI	10, 11
Tier II
Mutagenicity Testing (In vivo cytogenetics)
870.5385 870.5895	In vivo Mammalian Cytogenetics	CR	CR	TGAI	TGAI	13
Developmental Toxicity
870.3700	Prenatal developmental	CR	CR	TGAI	TGAI	9
Special Tests
880.3550	Immunotoxicity	CR	CR	TGAI	TGAI	12, 13
Applicator/User Exposure
875.1100	Dermal outdoor exposure	CR	CR	TGAI	TGAI	15
875.1200	Dermal indoor exposure	CR	CR	TGAI	TGAI	15
875.1300	Inhalation outdoor exposure	CR	CR	TGAI	TGAI	15
875.1400	Inhalation indoor exposure	CR	CR	TGAI	TGAI	15
875.1500	Biological monitoring	CR	CR	TGAI	TGAI	15
Tier III
Chronic Testing/Special Testing
880.3800	Immune response	CR	CR	TGAI	TGAI	14
870.3800	Reproduction and fertility effects	CR	CR	TGAI	TGAI	16
870.4100	Chronic oral - rodent and nonrodent	CR	CR	TGAI	TGAI	17
870.4200	Carcinogenicity - two species - rat and mouse preferred	CR	CR	TGAI	TGAI	18
870.5380	Mammalian spermatogonial chromosome aberration test	CR	CR	TGAI	TGAI	19
Special Testing
870.7200	Companion animal safety	CR	CR	NR	TGAI or EP	20

(e) Test notes. The following test notes are applicable to the data requirements for biochemical pesticides human health assessment as referenced in the last column of the table in paragraph (d) of this section.

1. Required unless the test material is a gas or highly volatile (vapor pressure >10−4torr (mm/Hg)).

2. Required unless the test material is corrosive to skin or has pH <2 or >11.5.

3. Required when the pesticide, under conditions of use, would result in respirable material (e.g., gas, volatile substance or aerosol/particulate), unless it is a straight chain lepidopteran pheromone.

4. Required if repeated contact with human skin is likely to occur under conditions of use.

5. Hypersensitivity incidents must be reported as adverse effects data.

6. Required for non-food uses that are likely to result in repeated oral exposure to humans.

7. Required to support uses involving purposeful application to the human skin or which would result in comparable prolonged human exposure to the product (e.g., insect repellents) and if any of the following criteria are met:

i. Data from a 90-day oral study are not required.

ii. The active ingredient is known or expected to be metabolized differently by the dermal route of exposure than by the oral route and the metabolite is of toxicological concern.

iii. The use pattern is such that the dermal route would be the primary route of exposure.

8. Required if there is a likelihood of significant levels of repeated inhalation exposure to the pesticide as a gas, vapor, or aerosol.

9. Required if the use of the product under widespread and commonly recognized practice may reasonably be expected to result in significant exposure to female humans (e.g., occupational exposure or repeated application of insect repellents directly to the skin). Tier II data is required on a different test species from Tier I data when developmental effects are observed in the first study and information on species-to-species extrapolation is needed.

10. Required to support nonfood uses if either:

i. The use is likely to result in significant human exposure; or

ii. The active ingredient (or its metabolites) is structurally related to a known mutagen or belongs to any chemical class of compounds containing a known mutagen. Additional mutagenicity tests that may have been performed plus a complete reference list must also be submitted. Subsequent testing may be required based on the available evidence.

11. Choice of assay using either:

i. Mouse lymphoma L5178Y cells, thymidine kinase (tk) gene locus, maximizing assay conditions for small colony expression or detection;

ii. Chinese hamster ovary (CHO) or Chinese hamster lung fibroblast (V79) cells, hypoxanthine-guanine phosphoribosyl transferase (hgprt) gene locus, accompanied by an appropriate in vitro test for clastogenicity; or

iii. CHO cells strains AS52, xanthine-guanine phosphoribosyl transferase (xprt) gene locus.

12. Required if there are effects on hematology, clinical chemistry, lymphoid organ weights, and histopathology are observed in the 90-day studies.

13. The micronucleus rodent bone marrow assay is preferred; however, rodent bone marrow assays using metaphase analysis (aberrations) are acceptable.

14. Required if adverse effects are observed in the Tier II immunotoxicity study. The protocol for evaluating adverse effects to the immune response should be developed after evaluating the effects noted in the immunotoxicity study.

15. These data are required when the data used for the human health assessment indicates that the biochemical may pose a potential hazard to the applicator/user.

16. Required if there is evidence of:

i. Endocrinological effects from the subchronic toxicity studies.

ii. Developmental effects in the prenatal developmental toxicity study(s), or

iii. Genotoxicity to mammals based on results from the mutagenicity tests.

The use of a combined study that utilizes the two-generation reproduction study in rodents (guideline 870.3800) as a basic protocol for the addition of other endpoints or functional assessments in the immature animal is encouraged.

17. Required if the potential for adverse chronic effects is indicated based on any of the following:

i. The subchronic effect level established in the following Tier I studies: 90-day oral toxicity study, 90-day dermal toxicity study, or 90-day inhalation toxicity study.

ii. The pesticide use pattern (e.g., rate, frequency, and site of application).

iii. The frequency and level of repeated human exposure that is expected.

18. Required if the product meets either of the following criteria:

i. The active ingredient (or any of its metabolites, degradation products, or impurities) produce(s) in Tier I subchronic studies a morphologic effect (e.g., hyperplasia or metaplasia) in any organ that potentially could lead to neoplastic change.

ii. Adverse cellular effects suggesting carcinogenic potential are observed in Tier II immunotoxicity and Tier III immune response study or in Tier II mammalian mutagenicity assays.

In addition, a 90-day range finding study in both rats and mice is required to determine the dose levels if carcinogenicity studies are required. If the mouse carcinogenicity study is not required, the 90-day mouse subchronic study is likewise not required.

19. Required if results from lower tiered mutation or reproductive studies indicate there is potential for chromosomal aberration to occur.

20. May be required if the product's use will result in exposure to domestic animals through, but not limited to, direct application or consumption of treated feed.

§ 158.2060 - Biochemical pesticides nontarget organisms and environmental fate data requirements table.

(a) General. (1) Sections 158.100 through 158.130 describe how to use this table to determine the terrestrial and aquatic nontarget organisms and fate data requirements for a particular biochemical pesticide product. Notes that apply to an individual test including specific conditions, qualifications, or exceptions to the designated test are listed in paragraph (e) of this section. In general, for all outdoor end-use products including turf, the following studies are required: one avian acute oral, one avian dietary, one acute freshwater fish, one acute freshwater invertebrate study, plant toxicity testing, and a honeybee acute contact study.

(2) The data in this section are not required for arthropod pheromones when applied at up to a maximum use rate of 150 grams active ingredient/acre/year except when the product is expected to be available to avian species (i.e., granular formulation).

(b) Use patterns. The terrestrial use pattern includes products classified under the general use patterns of terrestrial food crop, terrestrial feed crop, and terrestrial nonfood/nonfeed crop. The greenhouse use pattern includes products classified under the general use patterns of greenhouse food crop and greenhouse nonfood crop. The indoor use pattern includes products classified under the general use patterns of indoor food and nonfood use. The remaining terrestrial uses include: forestry and residential outdoor use. Data are also required for the general use patterns of aquatic food and nonfood crop use.

(d) Table. The following table shows the data requirements for biochemical pesticides nontarget organisms and environmental fate. The test notes are shown in paragraph (e) of this section.

Table—Biochemical Pesticides Nontarget Organisms and Environmental Fate Data Requirements

Guideline Number	Data Requirement	Use Patterns					Test Substance	Test Notes
		Terrestrial	Aquatic	Greenhouse	Forestry, Residential Outdoor	Indoor
		Food/Feed/Nonfood	Food/Nonfood	Food/Nonfood	Forestry, Residential Outdoor	Food/Nonfood
Tier I
Avian Testing
850.2100	Avian acute oral toxicity	R	R	CR	R	CR	TGAI, EP	1, 2, 3, 4
850.2200	Avian dietary toxicity	R	R	CR	R	CR	TGAI, EP	1, 2, 3, 4
Aquatic Organism Testing
850.1075	Fish acute toxicity, freshwater	R	R	CR	R	CR	TGAI, EP	2, 3, 4, 5
850.1010	Aquatic invertebrate acute toxicity, freshwater	R	R	CR	R	CR	TGAI, EP	2, 3, 5
Nontarget Plant Testing
850.4100	Terrestrial Plant Toxicity, Seedling emergence	R	R	NR	R	NR	TGAI, EP	5
850.4150	Terrestrial Plant Toxicity, Vegetative vigor	R	R	NR	R	NR	TGAI, EP	5
Insect Testing
880.4350	Nontarget Insect Testing	R	R	R	R	NR	TGAI	14
Tier II
Environmental Fate Testing
163-1 (835.1230)	Sediment and soil adsorption/desorption for parent and degradates	CR	CR	CR	CR	NR	TGAI	6
163-1 (835.1240)	Soil column leaching	CR	CR	CR	CR	NR	TGAI	6
163-2 (835.1410)	Laboratory volatilization from soil	CR	NR	CR	CR	NR	TEP	7
161-1 (835.2120)	Hydrolysis	CR	CR	CR	CR	NR	TGAI	6
161-1 (835.4100)	Aerobic soil metabolism	CR	NR	CR	CR	NR	TGAI	6
161-2 (835.2240)	Photodegradation in water	CR	CR	CR	CR	NR	TGAI	6
161-3 (835.2410)	Photodegradation on soil	CR	NR	CR	CR	NR	TGAI	6
162-2 (835.4200)	Anaerobic soil metabolism	CR	NR	NR	NR	NR	TGAI	6
162-4 (835.4300)	Aerobic aquatic metabolism	CR	CR	CR	CR	NR	TGAI	6
162-3 (835.4400)	Anaerobic aquatic metabolism	CR	CR	NR	NR	NR	TGAI	6
880.4425	Dispenser - water leaching	CR	NR	CR	CR	NR	EP	8
Nontarget Plant
850.4225	Seedling emergence	R	R	NR	R	NR	TGAI	9
850.4250	Vegetative vigor	R	R	NR	R	NR	TGAI	9
Tier III
Aquatic Fauna Chronic, Life Cycle, and Field Studies
850.1300 850.1400 850.1500	Freshwater fish/invertebrate testing	CR	CR	NR	CR	NR	TGAI	10
850.1025 850.1035 850.1045 850.1055 850.1350 850.1400 850.1500	Marine/Estuarine fish/invertebrate animal testing	CR	CR	NR	CR	NR	TGAI	10
850.1950	Aquatic field fish/invertebrate testing	CR	CR	NR	CR	NR	EP	10
Terrestrial Wildlife
850.2300	Avian Reproduction	CR	CR	NR	CR	NR	TGAI	11
850.2400	Wild mammal acute toxicity	CR	CR	NR	CR	NR	TGAI	11
850.2500	Terrestrial field testing	CR	CR	NR	CR	NR	EP	11
Beneficial Insects
850.3040	Field testing for Pollinators	CR	CR	NR	CR	NR	TEP	12
Nontarget Plants
850.4225 850.4250 850.4300 850.4450	Nontarget plant	CR	CR	NR	CR	NR	TGAI	13

(e) Test notes. The following test notes are applicable to the data requirements for biochemical pesticides nontarget organisms and environmental fate as referenced in the last column of the table contained in paragraph (d) of this section.

1. Required for the EP when any end-use formulation may contain other ingredients that may be toxic to nontarget organisms or to support arthropod pheromones that would be available to avian wildlife, (e.g., a granular product).

2. Tests for pesticides intended solely for indoor application would be required on a case-by-case basis, depending on use pattern, physical/chemical properties, production volume, and other pertinent factors.

3. Not required for any use groups if the pesticide is highly volatile (estimated volatility >5 × 10−5atm m 3/mol).

4. Preferred test species are Upland game, waterfowl, or passerine for avian acute oral toxicity studies; Upland game and waterfowl for avian dietary studies; and coldwater fish species for acute freshwater fish studies.

5. Required for the EP when the end-use formulation may contain other ingredients that may be toxic to nontarget organisms.

6. Required on a case-by-case basis when results from Tier I studies indicate adverse effects.

7. Required when results of any one or more of the nontarget organism studies in Tier I indicate potential adverse effects on nontarget organisms and the pesticide is to be applied on land. In view of methdological difficulties with the study of photodegradation in air, prior consultation with the Agency regarding the protocol is recommended before the test is performed.

8. Required when results of any one or more of the nontarget organism studies in Tier I indicate potential adverse effects on nontarget organisms and the pesticide is to be applied in a passive dispenser.

9. Required to support registration of known phytotoxicants, i.e., herbicides, desiccants, defoliants, and plant growth regulators.

10. Required if environmental fate characteristics indicate that the estimated environmental concentration of the pesticide in the aquatic environment is >0.01 of any EC50 or LC50 determined in the aquatic nontarget organism testing.

11. Required if either of the following criteria are met:

i. Environmental fate characteristics indicate that the estimated concentration of the pesticide in the terrestrial environment is >0.20 the avian dietary LC50 or equal to >0.20 the avian oral single dose LD50 (converted to ppm).

ii. The pesticide or any of its metabolites or degradation products are stable in the environment to the extent that potentially toxic amounts may persist in the avian or mammalian feed.

12. Required when results of Tier I nontarget organism studies indicate potential adverse effects on nontarget insects and results of Tier II tests indicate exposure of nontarget insects. Additional insect species may have to be tested if necessary to address issues raised by use patterns and potential exposure of important nontarget insect species, (e.g., threatened or endangered species).

13. Required if the product is expected to be transported from the site of application by air, soil, or water. The extent of movement would be determined by the results of the Tier II environmental fate studies.

14. Required depending on pesticide mode of action, method and timing of application, and results of any available efficacy data. Typically the honeybee acute toxicity guideline (guideline 850.3020) satisfies this requirement, however, additional nontarget insect species may have to be tested if necessary to address issues raised by use patterns and potential exposure of important nontarget insect species, (e.g., endangered species.)

§ 158.2070 - Biochemical pesticides product performance data requirements.

(a) General. Product performance data must be developed for all biochemical pesticides. Each applicant must ensure through testing that the product is efficacious when used in accordance with label directions and commonly accepted pest control practices. The Agency may require, on a case-by-case basis, submission of product performance data for any pesticide product registered or proposed for registration or amendment.

(b) Product performance data for each product that bears a claim against an invertebrate pest that is covered by subpart R of this part. The product performance data requirements and performance standards of subpart R of this part apply to biochemical products covered by this subpart. Product performance data must be submitted with any application for registration or amended registration. However, data requirements and the performance standards that determine the acceptability of data may be waived or modified on a case-by-case basis pursuant to the waiver provisions in § 158.45 and modification provisions in § 158.1707.

(c) Product performance data for each product that bears a public health pest claim, excluding those covered under paragraph (b). Product performance data must be submitted with any application for registration or amended registration, if the product bears a claim to control public health pests, such as pest microorganisms infectious to humans in any area of the inanimate environment, or a claim to control vertebrates, including but not limited to, rodents, birds, bats, canids, and skunks.

[87 FR 22484, Apr. 15, 2022]

§ 158.2080 - Experimental use permit data requirements—biochemical pesticides.

(a) Sections 158.2081 through 158.2084 describe the experimental use permit (EUP) data requirements for biochemical pesticides. Variations in the test conditions are identified within the test notes. Definitions that apply to all biochemical data requirements can be found in § 158.2000.

(b) For general information on the data requirement tables, see § 158.2010(b)-(f).

§ 158.2081 - Experimental use permit biochemical pesticides product chemistry data requirements table.

(a) General. (1) Sections 158.100 through 158.130 describe how to use this table to determine the product chemistry data requirements for a particular biochemical pesticide product. Notes that apply to an individual test and include specific conditions, qualifications, or exceptions to the designated test are listed in paragraph (e) of the section.

(2) Depending on the results of the required product chemistry studies, appropriate use restrictions, labeling requirements, or special packaging requirements may be imposed.

(b) Use patterns. Product chemistry data are required for all pesticide products and are not use specific.

(d) Table. The following table shows the data requirements for experimental use permit biochemical pesticides product chemistry. The test notes are shown in paragraph (e) of this section.

Table—EUP Biochemical Pesticides Product Chemistry Data Requirements

Guideline Number	Data Requirement	All Use Patterns	Test Substance		Test Notes
Guideline Number	Data Requirement	All Use Patterns	MP	EP	Test Notes
Product Identity and Composition
880.1100	Product identity and composition	R	TGAI, MP	TGAI, EP	1, 2
880.1200	Description of starting materials, production and formulation process	R	TGAI, MP	TGAI, EP	2, 3
880.1400	Discussion of formation of impurities	R	TGAI and MP	TGAI and EP	4
Analysis and Certified Limits
830.1700	Preliminary analysis	CR	TGAI and MP	TGAI and EP	5, 8
830.1750	Certified limits	R	MP	EP	6
830.1800	Enforcement analytical method	R	MP	EP	7
Physical and Chemical Characteristics
830.6302	Color	R	TGAI	TGAI	8
830.6303	Physical state	R	TGAI and MP	TGAI and EP	8
830.6304	Odor	R	TGAI	TGAI	8
830.6313	Stability to normal and elevated temperatures, metals and metal ions	R	TGAI	TGAI	8, 17
830.6315	Flammability	CR	MP	EP	9
830.6317	Storage stability	R	MP	EP	—
830.6319	Miscibility	CR	MP	EP	10
830.6320	Corrosion characteristics	R	MP	EP	—
830.7000	pH	CR	TGAI and MP	TGAI and EP	8, 11
830.7050	UV/Visible light absorption	R	TGAI	TGAI	—
830.7100	Viscosity	CR	MP	EP	12
830.7200	Melting point/melting range	CR	TGAI	TGAI	8, 13
830.7220	Boiling point/boiling range	CR	TGAI	TGAI	8, 14
830.7300	Density/relative density/bulk density	R	TGAI and MP	TGAI and EP	8, 18
830.7520	Particle size, fiber length, and diameter distribution	CR	TGAI	TGAI	8, 15
830.7550 830.7560 830.7570	Partition coefficient (n-Octanol /Water)	CR	TGAI	TGAI	16
830.7840	Water solubility	R	TGAI	TGAI	8
830.7950	Vapor pressure	R	TGAI	TGAI	8, 19

(e) Test notes. The following test notes are applicable to the data requirements for experimental use permit biochemical pesticides product chemistry and are referenced in the last column of the table in paragraph (d) of this section.

1. Data must be provided in accordance with § 158.320.

2. If the MP and EP are produced by an integrated formulation system (non-registered source), these data are also required on TGAI.

3. Data must be provided in accordance with § 158.325, § 158.330, and § 158.335.

4. Data must be provided in accordance with § 158.340.

5. Data must be provided in accordance with § 158.345. Also, required to support the registration of each manufacturing-use product (including registered TGAIs) and end-use products produced by an integrated formulation system. Data on other end-use products would be required on a case-by-case basis. For pesticides in the production stage, a preliminary product analytical method and data would suffice to support an experimental use permit.

6. Data must be provided in accordance with § 158.350.

7. Data must be provided in accordance with § 158.355.

8. If the TGAI cannot be isolated, data are required on the practical equivalent of the TGAI. EP testing may also be appropriate.

9. Required if the product contains combustible liquids.

10. Required if the product is an emulsifiable liquid and is to be diluted with petroleum solvents.

11. Required if the test substance is soluble or dispersible in water.

12. Required if the product is a liquid.

13. Required when the technical chemical is a solid at room temperature.

14. Required when the technical chemical is a liquid at room temperature.

15. Required for water insoluble test substances (>10−6g/l) and fibrous test substances with diameter ≥0.1 µm.

16. Required for organic chemicals unless they dissociate in water or are partially or completely soluble in water.

17. Data on the stability to metals and metal ions is required only if the active ingredient is expected to come in contact with either material during storage.

18. True density or specific density are required for all test substances. Data on bulk density is required for MPs or EPs that are solid at room temperature.

19. Not required for salts.

§ 158.2082 - Experimental use permit biochemical pesticides residue data requirements table.

(c) Key. R = Required; CR = Conditionally required; NR = Not required; MP = Manufacturing end-use product; EP = End-use product; TEP = Typical end-use product; TGAI = Technical grade of the active ingredient; Residue of concern = the active ingredient and its metabolites, degradates,and impurities of toxicological concern. All = All of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph (e) of this section, and apply to the individual tests in the following table:

(d) Data table. The following table shows the data requirements for biochemical pesticides residue. The test notes are shown in paragraph (e) of this section.

Table—EUP Biochemical Pesticides Residue Data Requirements

Guideline Number	Data Requirement	Use Patterns				Test Substance	Test Notes
		Terrestrial	Aquatic	Greenhouse Food	Indoor Food
		Food/Feed	Food	Greenhouse Food	Indoor Food
Supporting Information
860.1100	Chemical identity	CR	CR	CR	CR	TGAI	1, 2, 4
860.1200	Directions for use	CR	CR	CR	CR	—	1, 3, 4
Nature of Residue
860.1300	Nature of the residue in plants	CR	CR	CR	CR	TGAI	1, 4, 5, 6
860.1300	Nature of the residue in livestock	CR	CR	CR	CR	TGAI or plant metabolite	1, 7, 8, 9, 13
Magnitude of the Residue
860.1400	Potable water	NR	CR	NR	NR	TGAI	1, 11
860.1400	Fish	NR	CR	NR	NR	TGAI	1, 12
860.1400	Irrigated crops	NR	CR	NR	NR	TGAI	1, 13
860.1460	Food handling	NR	NR	NR	CR	TGAI	1, 14
860.1480	Meat/milk/poultry/eggs	CR	CR	CR	CR	TGAI or plant metabolites	1, 7, 8, 9
860.1500	Crop field trials	CR	CR	CR	CR	TEP	1, 3, 4
860.1520	Processed food/feed	CR	CR	CR	CR	TEP	1, 15
860.1540	Anticipated residues	CR	CR	CR	CR	Residue of concern	1, 9, 16
860.1550	Proposed tolerances	CR	CR	CR	CR	—	1, 17
860.1560	Reasonable grounds in support of the petition	CR	CR	CR	CR	—	1, 9
860.1650	Submittal of analytical reference standards	CR	CR	CR	CR	TGAI and residue of concern	9, 18

(e) Test notes. The following test notes are applicable to the data requirements for biochemical pesticides product chemistry and are referenced referenced in the last column of the table contained in paragraph (d) of this section.

2. The same chemical identity data are required for biochemical product chemistry data requirements,§ 158.2030 with an emphasis on impurities.

3. Required information includes crops to be treated, rate of application, number and timing of applications, preharvest intervals, and relevant restrictions.

5. Required unless it is an arthropod pheromone applied at a rate less than or equal to 150 grams active ingredient per acre.

7. Required when a pesticide is to be applied directly to livestock, to livestock premises, to livestock drinking water, or to crops used for livestock feed. If results from the plant metabolism study show differing metabolites in plants form those found in animals, an additional livestock metabolism study involving dosing with the plant metabolite(s) may also be required.

8. Livestock feeding studies are required whenever a pesticide residue is present in livestock feed or when direct application to livestock uses occurs.

9. Required if indoor use could result in pesticide residues in or on food or feed.

10. Data are required to determine whether FDA/USDA multiresidue methodology would detect and identify the pesticides and any metabolites.

11. Data are required whenever a pesticide may be applied directly to water, unless it can be demonstrated that the treated water would not be available for human or livestock consumption.

12. Data on fish are required for all pesticides applied directly to water inhabited, or which will be inhabited, by fish that may be caught or harvested for human consumption.

13. Data are required when a pesticide is to be applied directly to water that could be used for irrigation or to irrigation facilities such as irrigation ditches.

14. Data are required whenever a pesticide may be used in food/feed handling establishments.

15. Data on the nature and level of residue in processed food/feed are required when detectible residues could potentially concentrate on processing thus requiring the establishment of a separate tolerance higher than that of the raw agricultural commodity.

16 Anticipated residue data are required when the assumption of tolerance level residues would result in predicted exposure at an unsafe level of exposure. Data, using single serving samples of a raw agricultural commodity, on the level or residue in food as consumed would be used to obtain a more precise estimate of potential dietary exposure. These data may also include washing, cooking, processing or degradation studies as well as market basket surveys for a more precise residue determination.

17. The proposed tolerance must reflect the maximum residue likely to occur in crops, in meat, milk, poultry, or eggs.

18. Required when a residue analytical method is required.

§ 158.2083 - Experimental use permit biochemical pesticides human health assessment data requirements table.

(a) General. (1) Sections 158.100 through 158.130 describe how to use this table to determine the human health assessment data requirements for a particular biochemical pesticide product.

(2) The data in this section are not required for straight chain lepidopteran pheromones when applied up to a maximum use rate of 150 grams active ingredient/acre/year.

(d) Table. The following table shows the data requirements for experimental use permit biochemical pesticides human health assessment. The test notes are shown in paragraph (e) of this section.

Table—EUP Biochemical Pesticides Human Health Assessment Data Requirements

Guideline Number	Data Requirement	Use Patterns		Test Substance		Test Notes
Guideline Number	Data Requirement	Food	Nonfood	MP	EP	Test Notes
Tier I
Acute Testing
870.1100	Acute oral toxicity - rat	R	R	TGAI and MP	TGAI and EP	1
870.1200	Acute dermal toxicity	R	R	TGAI and MP	TGAI and EP	1, 2
870.1300	Acute inhalation toxicity - rat	R	R	TGAI and MP	TGAI and EP	3
870.2400	Primary eye irritation - rabbit	R	R	TGAI and MP	TGAI and EP	2
870.2500	Primary dermal irritation	R	R	TGAI and MP	TGAI and EP	1, 2
none	Hypersensitivity incidents	R	R	All	All	4
Subchronic Testing
870.3100	90-day oral (one species)	R	NR	TGAI	TGAI	—
Developmental Toxicity
870.3700	Prenatal developmental - rat preferably	R	CR	TGAI	TGAI	5
Mutagenicity Testing
870.5100	Bacterial reverse mutation test	R	CR	TGAI	TGAI	6
870.5300	In vivo mammalian cell assay	R	CR	TGAI	TGAI	6, 7
Tier II
Developmental Toxicity
870.3700	Prenatal developmental	CR	CR	TGAI	TGAI	5

(e) Test notes. The following test notes are applicable to the data requirements for experimental use permit biochemical pesticides human health assessment as referenced in the last column of the table in paragraph (d) of this section.

1. Required unless the test material is a gas or highly volatile (vapor pressure >10−4torr (mm/Hg)).

2. Required unless the test material is corrosive to skin or has pH <2 or >11.5.

4. Hypersensitivity incidents must be reported as adverse effects data.

5. Required if the use of the product under widespread and commonly recognized practice may reasonably be expected to result in significant exposure to female humans (e.g., occupational exposure or repeated application of insect repellents directly to the skin). Tier II data is required on a different test species from Tier I data when developmental effects are observed in the first study and information on species-to-species extrapolation is needed.

6. Required to support nonfood uses if either:

i. The use is likely to result in significant human exposure; or

ii. The active ingredient (or its metabolites) is structurally related to a known mutagen or belongs to any chemical class of compounds containing a known mutagen.

Additional mutagenicity tests that may have been performed plus a complete reference list must also be submitted. Subsequent testing may be required based on the available evidence.

7. Choice of assay using either:

i. Mouse lymphoma L5178Y cells, thymidine kinase (tk) gene locus, maximizing assay conditions for small colony expression or detection;

iii. CHO cells strains AS52, xanthine-guanine phosphoribosyl transferase (xprt) gene locus.

§ 158.2084 - Experimental use permit biochemical pesticides nontarget organisms and environmental fate data requirements table.

(b) Use patterns. The terrestrial use pattern includes products classified under the general use patterns of terrestrial food crop, terrestrial feed crop, and terrestrial nonfood/nonfeed crop. The greenhouse use pattern includes products classified under the general use patterns of greenhouse food crop and greenhouse nonfood crop. The indoor use pattern includes products classified under the general use patterns of indoor food and nonfood use. The remaining terrestrial uses include forestry and residential outdoor use. Data are also required for the general use patterns of aquatic food and nonfood crop use.

(d) Table. The following table shows the data requirements for experimental use permit biochemical pesticides nontarget organisms and environmental fate. The test notes are shown in paragraph (e) of this section.

Table—EUP Biochemical Pesticides Nontarget Organisms and Environmental Fate Data Requirements

Guideline Number	Data Requirement	Use Patterns					Test Substance	Test Notes
		Terrestrial	Aquatic	Greenhouse	Forestry, Residential Outdoor	Indoor
		Food/Feed/Nonfood	Food/Nonfood	Food/Nonfood	Forestry, Residential Outdoor	Food/Nonfood
Tier I
Avian Testing
850.2100	Avian acute oral toxicity	R	R	NR	R	NR	TGAI, EP	1, 2, 3
850.2200	Avian dietary toxicity	R	R	NR	R	NR	TGAI, EP	1, 2, 3
Aquatic Organism Testing
850.1075	Fish acute toxicity, freshwater	R	R	NR	R	NR	TGAI, EP	2, 3, 4
850.1010	Aquatic invertebrate acute toxicity, freshwater	R	R	NR	R	NR	TGAI, EP	2, 4

(e) Test notes. The following test notes are applicable to the data requirements for experimental use permit biochemical pesticides nontarget organisms and environmental fate as referenced in the last column of the table contained in paragraph (d) of this section.

2. Not required for any use groups if the pesticide is highly volatile (estimated volatility >5 × 10−5atm m 3/mol).

3. Preferred test species are: upland game, waterfowl, or passerine for avian acute oral toxicity studies; upland game or waterfowl for avian dietary studies; and coldwater fish for acute freshwater fish studies.

4. Required for the EP when the end-use formulation may contain other ingredients that may be toxic to nontarget organisms.

authority: 7 U.S.C. 136-136y; 21 U.S.C. 346a.

source: 72 FR 60957, Oct. 26, 2007, unless otherwise noted.

cite as: 40 CFR 158.2083